title: Carotid atherosclerotic plaques stabilize after stroke: insights into the natural process of atherosclerotic plaque stabilization.
abstract: OBJECTIVE
  Rupture of unstable atherosclerotic plaques is the pathological substrate for acute ischemic events. Underlying cellular and molecular characteristics of plaque rupture have been studied extensively. However, the natural course of symptomatic plaque remodeling after ischemic events is relatively unexplored.
  
  
  RESULTS
  Atherosclerotic carotid plaques were obtained from 804 symptomatic (stroke=204 and TIA=426) and asymptomatic (n=174) patients undergoing carotid endarterectomy. The presence of macrophages, smooth muscle cells (SMC), collagen, calcification, and lipid-core size were assessed histologically. At protein level, inflammatory mediators (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, interferon-gamma [INF-gamma], tumor necrosis factor-alpha [TNF-alpha], matrix degrading proteinases (MMPs), and an apoptosis marker (caspase-3) were determined. We associated plaque characteristics with time elapsed between the latest event and surgery. Early after stroke and TIA, plaques revealed an unstable phenotype. After stroke, the content of macrophages decreased significantly with time (P=0.02), whereas SMC content tended to increase. At protein level, IL-6, IL-8 expression levels and caspase activity strongly decreased after stroke or TIA.
  
  
  CONCLUSIONS
  Symptomatic carotid lesions remodel into more stable plaques over time after stroke. Changes in IL-6 and IL-8 and caspase preceded the decrease of macrophages. These temporal phenotypic plaque alterations should be taken into account for biomarker and therapeutic target validation studies using human atherosclerotic plaques.
authors.affiliation: Experimental Cardiology Laboratory, University Medical Centre Utrecht, Utrecht, The Netherlands. w.peeters-2@umcutrecht.nl
authors.forename: W
authors.initials: W
authors.lastname: Peeters
authors.forename: W E
authors.initials: WE
authors.lastname: Hellings
authors.forename: D P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: J P P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: F L
authors.initials: FL
authors.lastname: Moll
authors.forename: A
authors.initials: A
authors.lastname: Vink
authors.forename: G
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D017209:Apoptosis; D050197:Atherosclerosis / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D002114:Calcinosis / Q000473:pathology; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D053148:Caspase 3 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D016894:Endarterectomy, Carotid; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D020782:Matrix Metalloproteinases / Q000378:metabolism; D058225:Plaque, Amyloid / Q000201:enzymology / Q000473:pathology*; D020521:Stroke / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen; D053148:Caspase 3; D020782:Matrix Metalloproteinases